CN1205474C - Biosensor - Google Patents
Biosensor Download PDFInfo
- Publication number
- CN1205474C CN1205474C CNB028018796A CN02801879A CN1205474C CN 1205474 C CN1205474 C CN 1205474C CN B028018796 A CNB028018796 A CN B028018796A CN 02801879 A CN02801879 A CN 02801879A CN 1205474 C CN1205474 C CN 1205474C
- Authority
- CN
- China
- Prior art keywords
- utmost point
- pair
- effect
- substrate
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000000758 substrate Substances 0.000 claims abstract description 64
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 30
- 108090000790 Enzymes Proteins 0.000 claims abstract description 10
- 102000004190 Enzymes Human genes 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims description 82
- 230000027756 respiratory electron transport chain Effects 0.000 claims description 26
- 230000035945 sensitivity Effects 0.000 abstract description 6
- 230000033116 oxidation-reduction process Effects 0.000 abstract 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 39
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 37
- 239000008103 glucose Substances 0.000 description 37
- 238000000034 method Methods 0.000 description 18
- 239000001301 oxygen Substances 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
- 239000004020 conductor Substances 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- -1 potassium ferricyanide Chemical compound 0.000 description 7
- 239000011159 matrix material Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229910000510 noble metal Inorganic materials 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 108010015776 Glucose oxidase Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000000276 potassium ferrocyanide Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 239000004366 Glucose oxidase Substances 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical class [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 229940116332 glucose oxidase Drugs 0.000 description 2
- 235000019420 glucose oxidase Nutrition 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000001259 photo etching Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 108010025188 Alcohol oxidase Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010089254 Cholesterol oxidase Proteins 0.000 description 1
- 229920000896 Ethulose Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010050375 Glucose 1-Dehydrogenase Proteins 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 108010073450 Lactate 2-monooxygenase Proteins 0.000 description 1
- 239000004640 Melamine resin Substances 0.000 description 1
- 229920000877 Melamine resin Polymers 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001807 Urea-formaldehyde Polymers 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- HGAZMNJKRQFZKS-UHFFFAOYSA-N chloroethene;ethenyl acetate Chemical compound ClC=C.CC(=O)OC=C HGAZMNJKRQFZKS-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000003411 electrode reaction Methods 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000011810 insulating material Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920001225 polyester resin Polymers 0.000 description 1
- 239000004645 polyester resin Substances 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 150000004059 quinone derivatives Chemical class 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003375 selectivity assay Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229920005992 thermoplastic resin Polymers 0.000 description 1
- 239000004634 thermosetting polymer Substances 0.000 description 1
- 229920006337 unsaturated polyester resin Polymers 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/001—Enzyme electrodes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/001—Enzyme electrodes
- C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
- C12Q1/006—Enzyme electrodes involving specific analytes or enzymes for glucose
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
Abstract
A high sensitivity biosensor which responds well even to a trace of sample. The biosensor comprises a first insulating substrate having a working electrode branched into a plurality of pieces and a first counter electrode branched into a plurality of pieces with respective pieces being arranged alternately, a second insulating substrate having a second counter electrode and disposed oppositely to the first insulating substrate, a reagent system containing an oxidation-reduction enzyme, and a sample supply passage formed between the first and second insulating substrates, wherein the pieces of the working electrode and the first counter electrode arranged alternately, the second counter electrode and the reagent system are exposed to the sample supply passage.
Description
Technical field
The present invention relates to rapidly and the biology sensor of contained matrix in the quantitative sample accurately.
Background technology
As carbohydrate quantitative analysis methods such as sucrose, glucose, developed with methods such as optical activity meter method, colourimetry, reductometry and various chromatographys.But no matter to what kind of carbohydrate, these method specificitys are not too high, so precision is relatively poor.If with the optical rotation meter method in these methods, operation is simple, and still, during operation, temperature influence is big, so optical rotation meter method is improper usually as the method for people at local simple quantitative carbohydrates such as families.
In recent years, utilize various types of biology sensors of the specificity catalytic action that enzyme has to be developed.
Below, just the glucose quantitation method as sample mesostroma sizing technique one example is illustrated.What generally everybody knew is glucose oxidase (EC 1.1.3.4: following province is GOD slightly) and oxygen electrode or the method for hydrogen peroxide electrode (for example, " バ ィ ォ セ Application サ one (biology sensor) " Talk Talk society of Suzuki volume Monday publishes) that is to use enzyme as electrochemical glucose quantitation method.
GOD optionally is oxidized to the D-glucopyrone to oxygen as electron transfer mediator with matrix β-D-glucose.Under the situation that oxygen exists, in the oxidation reaction process, oxygen is reduced into hydrogen peroxide by GOD.The reduction of coming this oxygen of instrumentation by oxygen electrode, or the recruitment of coming the instrumentation hydrogen peroxide by the hydrogen peroxide electrode.Because the recruitment of the reduction of oxygen and hydrogen peroxide and the glucose amount in the sample are proportional, so can come quantitative glucose from the reduction of oxygen or the recruitment of hydrogen peroxide.
In said method, utilize the enzyme reaction specificity, accurately the glucose in the quantitative sample.But said method have measurement result can be subjected to sample the shortcoming of influence of oxygen containing concentration, under the situation that does not have oxygen to exist in the sample, just can not measure, this also can infer out from its course of reaction.
, developed without oxygen as electron transfer mediator for this reason, and with organic compounds such as the potassium ferricyanide, ferrocene derivatives, quinone derivatives and the metal complex novel glucose sensor as electron transfer mediator.The substance of going back of the electron transfer mediator that such sensor will generate as the result of enzyme reaction is extremely gone up oxidation in effect, and the oxidation current amount is obtained contained concentration of glucose in the sample thus.At this moment, to carrying out the reduction of electron transfer mediator oxysome on extremely, generate the also reaction of substance of electron transfer mediator.By replacing oxygen as electron transfer mediator with above-mentioned organic compound and metal network and thing, just can under steady state (SS), correctly be carried in known quantity GOD and these electron transfer mediators on the electrode, form reagent layer, and can not be subjected to that oxygen concentration influences in the sample, quantitative glucose accurately.In this case, owing to can also make the reagent layer that contains aerobic and electron transfer mediator with near integrated under the dry status with electrode system, so, receive numerous concerns in recent years based on the disposable glucose sensor of this technology.Its typical example is a disclosed biology sensor in No. the 2517153rd, the Japan special permission communique.Use disposable glucose sensor, only need to inject sample in dismountable sensor, just can measure concentration of glucose with analyzer at an easy rate toward being connected with analyzer also.
By having used the assay method of above-mentioned glucose sensor, just can easily obtain the substrate concentration in the microlitre order of magnitude sample.But in recent years, each side is expecting to develop a kind of biology sensor that can determine than 1 microlitre denier sample still less.Existing electrochemica biological sensor, when measuring the denier sample, the denier because the glucose amount in the sample becomes is so the situation that the sensitivity of measurement result descends occurs.
Therefore, on substrate, dispose 2 biology sensors that replace the approximate comb shape electrode of a plurality of branches of arranging and constituting by branch tablet with regard to developing.Fig. 7 shows near the sectional view of electrode system of this biology sensor.The biology sensor of the type, be disposed on the 1st electrode 1 of substrate 5, the oxysome of the electron transfer mediator that generates through oxidation just may be reduced on the 2nd electrode 3 of adjacency and revert to goes back substance, and this goes back substance also may be oxidized on the 1st electrode 1 of adjacency once more.Therefore, rise by the current value that is flowing on the 1st electrode 1, this sensor can come quantitative glucose with the sensitivity better than existing biology sensor.
Such technology not only is confined to quantitative glucose, also may be applied in contain in the sample other matrix quantitatively on.
But in order to obtain the necessary sample size of more micro-ization when measuring, each side is expecting to have a kind of more highly sensitive biology sensor in recent years.
Therefore, a kind of when measuring the sample size of denier even the object of the invention provides, the also high-sensitivity biological sensor that can well be replied.
Summary of the invention
Biology sensor of the present invention has the 1st insulativity substrate that is branched off into a plurality of effect utmost points and is branched off into the 1st pair of a plurality of utmost points, each branch tablet is alternately arranged, have the 2nd pair of utmost point, be disposed at the 1st insulativity substrate relative position on the 2nd insulativity substrate, contain the reagent system of oxidoreducing enzyme and be formed on sample supply path between the 1st and the 2nd insulativity substrate, the effect utmost point of alternately arranging in supply passageway and the branch tablet of the 1st pair of utmost point, the 2nd pair of utmost point and reagent system expose.
In aforementioned sample supply path, the 2nd pair extremely preferably be configured in act on extremely relative position on.
The invention provides a kind of the 1st insulativity substrate that is branched off into a plurality of the 1st effect utmost points and is branched off into the 1st pair of a plurality of utmost points, each branch tablet is alternately arranged that has, have be branched off into a plurality of the 2nd effect utmost points and be branched off into the 2nd pair of a plurality of utmost points, with the 2nd insulativity substrate that each branch tablet is alternately arranged, contain the reagent system of oxidoreducing enzyme and the biology sensor that is formed on the sample supply path between the 1st and the 2nd insulated substrate.The branch tablet and the reagent system of the 1st effect utmost point of alternately arranging in described sample supply path and the branch tablet of the 1st pair of utmost point, the 2nd effect utmost point of alternately arranging and the 2nd pair of utmost point expose.
Preferably the 2nd pair of utmost point is configured on the position extremely relative with the 1st effect, and the 2nd effect utmost point be configured in the 1st pair of extremely relative position on.
Description of drawings
Fig. 1 is the exploded perspective view of removing reagent layer of glucose sensor one embodiment of the present invention.
Fig. 2 is the sectional view that shows the electrode spread in the same sensor sample supply path.
Fig. 3 is another the routine sectional view that shows the electrode spread in the sensor sample supply path.
Fig. 4 is the exploded perspective view of removing reagent layer of another embodiment of biology sensor of the present invention.
Fig. 5 is the sectional view that shows the electrode spread in the same sensor sample supply path.
Fig. 6 is the exploded perspective view of removing reagent layer of the another embodiment of biology sensor of the present invention.
Fig. 7 is the sectional view that shows that existing biological sensor electrode is arranged.
Fig. 8 is the circuit structure calcspar that shows the determinator that sensor is installed of an embodiment of the present invention.
Fig. 9 is the circuit structure calcspar that shows the determinator that sensor is installed of another embodiment of the present invention.
Implement best mode of the present invention
Following with reference to accompanying drawing just the embodiment of biology sensor of the present invention be illustrated.
The shape and structure of the 1st substrate and the 2nd substrate etc., the shape of electrode and material, the number of branch tablet is not subjected to the restriction of embodiment shown below.
Fig. 1 is the longitudinal sectional drawing of removing reagent layer and interfacial agent layer of present embodiment glucose sensor.
The 1st substrate that 10 expressions are made of the electrical insulating property material.On this substrate 10,, formed by the effect utmost point 11 that is branched off into a plurality of approximate comb shapes and lead 12 thereof and be branched off into the 1st pair of utmost point 13 of a plurality of approximate comb shapes and the electrode system that lead 14 constitutes by photoetching process.Concrete grammar is: for example with the palladium sputter to substrate, cover this palladium film with diaphragm, then, add the mask identical shaped with electrode system, after the video picture that the etching of palladium film is last through exposure, remove diaphragm, just form the electrode system of setting shape.In the drawings, the effect utmost point 11 and the 1st pair of utmost point are respectively represented with 6 branch tablets, but are not limited thereto.Shown in the embodiment, the effect utmost point 11 and the 1st pair of utmost point also can be made of several 10 branch tablets as described later.On the 2nd substrate 30 that constitutes by the electrical insulating property material, palladium is splashed on this substrate and forms the 2nd pair of utmost point 33 and lead 34 thereof.The 2nd substrate 30 has airport 35.On the 1st substrate 10, for the end with this device contacts with the lead 34 of the 2nd pair of utmost point, have via 17, and, on the 2nd substrate 30, have via 36 and 37 for the end that makes device is connected with the lead 12 of the effect utmost point and the lead 14 of the 1st pair of utmost point 13.
Has the otch 21 that forms sample supply path described later on the dividing plate 20 that constitutes by insulating material.After being pasted and fixed on this dividing plate 20 on the 1st substrate 10, drip the reagent layer forming liquid on electrode system from otch 21, drying forms reagent layer, and this reagent layer includes the oxidoreducing enzyme GOD and the electron transfer mediator potassium ferricyanide.On reagent layer, be preferably formed as the interfacial agent layer that contains interfacial agent lecithin.
Then, the 1st substrate 10 that will be combined with dividing plate 20 according to the position shown in dot-and-dash line relation among Fig. 1 is connected with the 2nd substrate 30 and is assembled into glucose sensor.Then, between the 1st substrate and the 2nd substrate,, form the sample supply path in otch 21 parts of dividing plate 20.This sample supply path is the sample supply mouth with the open end 23 of otch 21, is terminal part with the airport 35 of the 2nd substrate 30.
In this sample supply path, electrode system is configured on the relative position with the 2nd pair of utmost point, and, determine by dividing plate 20 in the face of the area (electrode area) of sample supply path with the spacer function utmost point 11, the 1st pair of utmost point 13 and the 2nd pair of utmost point 33.
Following with reference to Fig. 8, illustrate with this sensor determination determination of glucose device.
Fig. 8 left side is depicted as the sensor 70.In the drawings, effect polar conductor 12, the 1st pair of polar conductor 14 and the 2nd pair of polar conductor 34 only are shown.On the other hand, determinator 71 has and above-mentioned lead 12,14 and 34 connectors that are connected respectively 72,74 and 84.Connector 84 is connected with connector 74 through switch 76, by switch 75 connector 84,74 is connected with reference potential generation circuit 77.Connector 72 is connected with current/voltage translation circuit 78 with potential generating circuit 82.Current/voltage translation circuit 78 be connected on the reference potential generation circuit 77 to benchmark very, apply positive potential when effect is extremely gone up, will change voltage output into by electrorheological at the effect utmost point with between to the utmost point.With A/D translation circuit 79 this output voltage is transformed into pulse, and CPU80 calculates the matrix content in the sample according to the pulse by 79 outputs of A/D translation circuit, this calculated value is represented with LCD81.
By above-mentioned sensor 70 is configured on the determinator 71, closes determinator switch 76, make the 1st pair of utmost point 13 and the 2nd pair of utmost point 33 short circuits, and while off switch 75.Contact with the sample supply mouth 23 of sensor end as the sample that will contain glucose, because capillarity, sample can arrive the reagent layer in the sample supply path at an easy rate.As detect sample and arrived electrode system, determinator just starts, and timer picks up counting.Reagent layer one is dissolved in the sample, and glucose is just by the GOD oxidation, and meanwhile, the electron transfer mediator potassium ferricyanide is reduced into potassium ferrocyanide.Through reasonable time, with to benchmark very, voltage 300mv is applied on the effect utmost point 11 by potential generating circuit 82 after device begins to start, at the effect utmost point 11 and the electric current that has the potassium ferrocyanide oxidation between to the utmost point pass through.The following running of the current/voltage translation circuit 78 by determinator is expressed concentration of glucose based on above-mentioned current value with LCD81.
Figure 2 shows that at the electrode system of present embodiment biology sensor nearby with the flow state of the electric current of electron transfer mediator oxidation.In the present embodiment, the effect utmost point 11 and more than 13 ground of the 1st pair of utmost point branch, these branch tablets are alternately arranged, and form electrode system, in the relative direction of this electrode system, dispose the 2nd pair of utmost point 33.By such formation, oxidized and the oxysome electron transfer mediator that generates is reduced on the 1st pair of utmost point 13 of adjacency on the effect utmost point 11 that is disposed on the 1st substrate 10, meanwhile, the substance of going back at the electron transfer mediator that spreads on the direction vertical with the effect utmost point 11 also is being disposed on the 2nd pair of utmost point 33 on the 2nd substrate 30 and is being reduced, and reverts to and goes back substance.In addition, because the diffusion layer growth that effect is extremely gone up is suppressed, the concentration of the redox kind on the 2nd pair of utmost point 33 just is reflected in replying of sensor.Compare owing to above-mentioned these reasons and existing biology sensor, replying of present embodiment biology sensor improved.
Here, the 2nd pair extremely preferably only be configured in act on extremely relative position on, that is, as shown in Figure 3,, form comb shape with a plurality of branch tablet 33a with the 2nd pair of utmost point 33 finishing.In the sample supply path, the branch tablet 33a of the 2nd pair of utmost point is placed on and acts on the utmost point branch tablet relative direction.Because like this, the 2nd pair of utmost point current density nearby directly over the effect utmost point becomes more high, can think that the concentration of the reduced form electron transfer mediator near the 2nd pair of utmost point can increase.Because replying of sensor exists with ... reduced form electron transfer mediator concentration, so as a result of, just can quantitative in high sensitivity matrix.
Embodiment 2
Fig. 4 is the exploded perspective view that the present embodiment glucose sensor has been removed reagent layer and interfacial agent layer.
With the order identical, on the 1st substrate 40, form by the 1st effect utmost point the 41, the 1st effect polar conductor 42 that is branched off into a plurality of approximate comb shapes, be branched off into the 1st electrode system that the 1st pair of utmost point 43 of a plurality of approximate comb shapes and its lead 44 constitute with embodiment 1.On the 2nd substrate 60, form by the 2nd effect utmost point the 61, the 2nd effect polar conductor 62 that is branched off into a plurality of approximate comb shapes, be branched off into the 2nd electrode system that a plurality of the 2nd pair of utmost points 63 and its lead 64 constitute.As embodiment 1, the effect utmost point and not limit by the figure registration to the branch tablet number of the utmost point.Airport 65 is formed on the 2nd substrate 60.For end and the lead 62 of the 2nd pair of utmost point and the lead 64 of the 2nd effect utmost point with device is connected, on the 1st substrate, form via 48 and 49, equally, for the device end is connected with the lead 42 of the 1st effect utmost point and the lead 44 of the 1st pair of utmost point, on the 2nd substrate 60, via 68 and 69 have been opened.
Then, on the 1st substrate 40, after subsides add dividing plate 50, form reagent layer, according to the relation of the dot-and-dash line position shown in Fig. 4 the 2nd substrate 60 is coupled together and make glucose sensor.Have the otch 51 that forms the sample supply path on the dividing plate 50, the open end 52 of its otch 51 becomes the sample supply mouth.
As above-mentioned making, otch 51 by dividing plate 50, between the 1st substrate 40 and the 2nd substrate 60, form the sample supply path, then, as shown in Figure 4, the 2nd pair of utmost point 63 is configured on the relative position of the 1st effect utmost point 41 in the sample supply path, and the 2nd effect utmost point 61 is configured on the relative position of the 1st pair of utmost point 43.Otch 51 by dividing plate 50 is determined the 1st effect utmost points 41, the 1st pair of utmost point the 43, the 2nd effect utmost point 61 and the 2nd pair of utmost point 63 area (electrode area) in the face of the sample supply path.The 1st effect utmost point 41 and the 2nd that forms the sensor of present embodiment with the effect utmost point 11 equal electrode areas with embodiment 1 acts on the aggregated electrode area of the utmost point 61.But, compare owing on the 2nd substrate, disposing the 2nd effect utmost point 61 and embodiment 1 sensor, just form more highdensity electrode system, therefore, compare with embodiment 1, can dwindle the size of otch 51, sample size is reduced.
Here, the 2nd pair extremely preferably be configured in the 1st the effect utmost point relative position on, and the 2nd the effect utmost point also preferably be configured on the relative position of the 1st pair of utmost point.
Figure 5 shows that the electrode spread in the biology sensor sample supply path of present embodiment.Be configured in the effect utmost point 41 of the 1st on the 1st substrate 40 and the 1st pair of utmost point 43 with alternately arranging each, be disposed at the effect utmost point 61 of the 2nd on the 2nd substrate 60 and the 2nd pair of utmost point 63 with each, and, the 1st the effect utmost point 41 and the 2nd pair of utmost point 63 is on the relative direction, and the 1st pair of utmost point 43 and the 2nd effect utmost point 61 also are on the relative direction.Therefore, compare with biology sensor shown in Figure 2, under the long-pending identical situation of resultant action pole-face, just more thickly configured electrodes is.Thus, because can reduce sample supply path volume, just can reduce the sample size of detection bodies.
Fig. 6 is the exploded perspective view that the present embodiment glucose sensor has been removed reagent layer and interfacial agent layer.
Present embodiment and embodiment 1 difference are to form the reference utmost point 15 and its lead 16 on the 1st substrate 10, and for 2 ends of device are connected with the lead 16 of the effect polar conductor 12 and the reference utmost point 15 separately, on the 2nd substrate 30, form via 38, in addition, all the other structures are all identical with embodiment 1.
Just measuring the determination of glucose device with this sensor below with reference to Fig. 9 is illustrated.
Show the sensor 80 in Fig. 9 left side.Effect polar conductor the 12, the 1st reference polar conductor 16 only is shown among the figure, to polar conductor 14 and the 2nd pair of polar conductor 34.On the other hand, determinator 81 has respectively the connector 72,96,74 and 84 that is connected with 34 with above-mentioned lead 12,16,14, and wherein connector 74 is connected with current occuring circuit 97 with 84; Potential generating circuit 82 is connected with connector 72 with current/voltage translation circuit 78.Current/voltage translation circuit 78, A/D translation circuit 79 and CPU80 carry out identical running as the determinator of explanation in the embodiment 1.
By above-mentioned sensor 80 is assemblied on the determinator 81, contacts with sensor end sample supply 23 as containing the glucose sample, because capillarity, sample can easily arrive the reagent layer in the sample supply path.As detect sample and arrived electrode system, determinator starts, and timer just picks up counting.Through reasonable time, be benchmark with the reference utmost point 15 after device begins to start, 300mv voltage is applied on the effect utmost point 11 by potential generating circuit 82, just has the electric current with the potassium ferrocyanide oxidation to pass through at the effect utmost point 11 with between to the utmost point.Identical with embodiment 1, by the running of current/voltage translation circuit below 78 of determinator, express concentration of glucose based on above-mentioned current value with LCD81.
With the reason identical with embodiment 1, the present embodiment biology sensor is compared with the prior biological sensor, and its response value has improved.In addition, compare,, stablized the current potential of the effect utmost point 11, therefore, just may measure more accurately owing to be provided with the reference utmost point 15 with the sensor that does not dispose the reference utmost point.
The present invention is as the 1st substrate and the 2nd substrate, as long as use the material that has enough rigidity when having electrical insulating property, preservation and mensuration.For example can use thermoplastic resins such as tygon, polystyrene, Polyvinylchloride, polyamide, saturated polyester resin, or thermoset resin such as urea resin, melamine resin, phenolics, epoxy resin, unsaturated polyester resin.From with electrode adaptation angle, the most handy polyethylene terephthalate.Dividing plate also available and the 1st substrate and the same material of the 2nd substrate.In addition, dividing plate also can play the effect with the bonding agent of the 1st substrate and the 2nd base plate bonding.
As the effect utmost point, can use when the electron transfer mediator oxidation himself not oxidized conductive material.As to the utmost point, as long as just passable with the common used conductive material of noble metal such as palladium, gold and platinum and graphite etc.Wherein, preferred noble metal is that principal ingredient is used as acting on the utmost point and to the utmost point.Like this, machined electrode more subtly just, thus, just may high precision int and reduce the amount of detection bodies.
In the present embodiment, with the method for making of photoetching process, but be not limited in this respect as electrode system.For example: the noble metal sputter is formed noble metal film to substrate,, thereby just can form electrode with this noble metal film of laser reconditioning.
As oxidoreducing enzyme, can use enzyme material, for example: sucrose dehydrogenasa, glucose oxidase, glucose dehydrogenase, alcohol oxidase, Lactate Oxidase, cholesterol oxidase, xanthine oxidase, amino acid oxidase etc. corresponding to contained determination object matrix in the sample.
Hydrophilic macromolecule also can be contained in reagent system.Can use various materials as hydrophilic macromolecule, for example: the polymkeric substance of polyaminoacid, polystyrolsulfon acid, gelatin and derivant thereof, polyacrylic acid and salt thereof, polymethylacrylic acid and salt thereof, starch and derivant thereof, maleic anhydride or its salt of hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, ethylhydroxyethylcellulose, carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol (PVA), polylysine etc.Wherein preferably carboxymethyl cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose.
Below, illustrate in greater detail the present invention by embodiment.
According to the structure fabrication glucose sensor shown in the embodiment 1.In the present embodiment, the effect utmost point 11 and the 1st pair of utmost point 13 are that every wide is the comb shape electrode that 5 μ m branch tablets are formed with 1 μ mm at interval by 65, the effect utmost point and the utmost point alternately arranged at interval with 5 μ m.
After will containing on the electrode system that GOD and potassium ferricyanide aqueous solution drop in the 1st substrate 1, the dry reagent layer that forms in addition, on reagent layer, forms the interfacial agent layer that contains interfacial agent lecithin.
Then, containing the glucose certain quantity solution, measure concentration of glucose wherein as sample.In the present embodiment, the 1st pair of utmost point 13 and the 2nd pair of utmost point 33 short circuits are used as the utmost point.Sample is supplied in the sample supply path from sample supply mouth 23, supply with sample after 25 seconds, apply the voltage of 300mv benchmark very for the effect utmost point, apply voltage after 5 seconds, the mensuration effect utmost point 11 and to the current value that passes through between the utmost point, convert this current value to magnitude of voltage by current/voltage translation circuit 78, this magnitude of voltage just becomes the index by size of current between the expression electrode.The result just can observe with sample in the proportional current response of concentration of glucose.
As a comparative example, only be used as also can carrying out the same mensuration of replying to the sensor of the utmost point with the 1st pair of utmost point 13.In the case, close swap switch 75, and switch 76 is leaving.
Like this, just observed embodiment 1 and comparative example two sensors with sample in the proportional current response of concentration of glucose.But the biology sensor of embodiment 1 can obtain the response value higher than the biology sensor of comparative example.Be considered to because in embodiment 1 as the high sensitivity reason, the substance of going back of the electron transfer mediator that also can the effect by the 2nd pair of utmost point will spread on the vertical direction of the effect utmost point is extremely gone up oxidized at the 2nd pair, and owing to suppressed the diffusion layer growth in effect on extremely, the concentration of the 2nd pair of redox kind that extremely goes up can become by sensor replys the cause that is reflected etc.
Embodiment 2
According to the structure fabrication glucose sensor shown in the embodiment 2.In the present embodiment, the 1st effect utmost point 41 and the 2nd pair of utmost point 63 are to have 32, and every width is 5 μ m, is spaced apart the comb shape electrode of the branch tablet of 15 μ m, the 2nd effect utmost point 61 and the 1st pair of utmost point 43 are that to have 33 every width be 5 μ m, are spaced apart the comb shape electrode of the branch tablet of 15 μ m.The 1st effect utmost point is alternately arranged with 5 μ m interval and the 1st pair of utmost point, and the 2nd effect utmost point and the 2nd pair of utmost point also are with 5 μ m alternately arrangement at interval.Thus, the 1st the effect utmost point and the 2nd pair of utmost point also has the 2nd effect utmost point and the 1st pair of utmost point, all separately to configuration.The formation of reagent layer and interfacial agent layer is identical with embodiment 1.
As embodiment 1, the solution that contains a certain amount of glucose as sample, is measured concentration of glucose wherein.In the present embodiment, the 1st pair of utmost point 43 and the 2nd pair of utmost point 63 short circuits are formed the utmost point, with the 2nd effect utmost point 41 and the 1st effect utmost point 61 short circuits formation effect utmost point.From sample supply mouth 52 with sample supply in the sample supply path, after 25 seconds,, apply 300mv voltage and extremely go up in effect with to benchmark very, the result is can obtain than using the higher response value of comparative example sensor among the embodiment 1.
Except adding the reference utmost point 15 as shown in Figure 6, remaining all with the embodiment 1 the same sensor of making.According to shown in Figure 9 sensor is installed on the determinator, will be in sample supply sample supply path from sample supply mouth 23, sample supply is after 25 seconds, with the reference utmost point 15 is that benchmark applies 300mv voltage on the effect utmost point 11, apply voltage after 5 seconds, the mensuration effect utmost point 11 and to the current value that passes through between the utmost point is transformed to magnitude of voltage by current/voltage translation circuit 78 with this current value.
In the above-described embodiments, the effect utmost point and be 10 μ m to every branch tablet width of the utmost point, and the effect utmost point on the same substrate and be 5 μ m to the distance of the utmost point still, are not limited in this respect.In addition, from the supplying to voltage application will be arranged 25 seconds of sample, to this also without limits, enzyme reaction carry out time requirement have can obtain with the degree of the concentration dependent current response of sample mesostroma just, be preferably in below 180 seconds.
Electrode system is applied the voltage of 300mv, but unrestricted to this, make the voltage of electron transfer mediator as long as have in the extremely enterprising column electrode reaction of effect.
For the effect utmost point with to the distance of the utmost point, be formed on the effect utmost point branch tablet on the same substrate and the distance between the utmost point branch tablet be preferably in the scope of 1-50 μ m: the distance between electrodes of the electrode of the 1st substrate and the 2nd substrate is decided by the thickness of dividing plate, and the thickness of dividing plate is preferably in the scope of 1-50 μ m.
In an embodiment, be used as electron transfer mediator, but be not limited in this respect, also can use 1,4-benzoquinone, azophenlyene Methylsulfate, methylenum careuleum, ferrocene derivatives etc. with the potassium ferricyanide.In addition, under the situation of oxygen, also can obtain current response as electron transfer mediator.Also can use the above-mentioned two or more electron transfer mediators that are used as,
In the foregoing description, make the 1st pair of utmost point and the 2nd pair of utmost point short circuit forming to the utmost point, but unrestricted to this, also can make the 1st pair of utmost point and the 2nd pair of extremely independent running.For example: apply the location that can make the electron transfer mediator reduction for the 1st pair of utmost point, even and only to use the 2nd pair of utmost point to be used as the utmost point also be feasible.
In the foregoing description, used β-D-D/W as sample, but be not limited in this respect.For example, also can adopt the body sample of the life of whole blood, blood plasma, serum, interstitial fluid, saliva and urine etc.Sample is that the situation of whole blood is, for example, and the blood capillary or venous blood, the arterial blood etc. that obtain by puncture finger tip and wrist skin.
The possibility of using on the industry
By the invention described above, even can make atomic sample size, the height that also can well be replied The sensitivity biology sensor.
Claims (4)
1. biology sensor, it comprises having the 1st insulativity substrate that is branched off into a plurality of effect utmost points and is branched off into the 1st pair of a plurality of utmost points, each branch tablet is alternately arranged, have the 2nd pair of utmost point, be disposed at the 1st insulativity substrate relative position on the 2nd insulativity substrate, contain the reagent system of oxidoreducing enzyme and electron transfer mediator and be formed on sample supply path between the 1st and the 2nd insulativity substrate, the effect utmost point of alternately arranging in supply passageway and the branch tablet of the 1st pair of utmost point, the 2nd pair of utmost point and reagent system expose.
2. biology sensor according to claim 1 is characterized in that, in described sample supply path, the 2nd pair of utmost point only be configured in act on extremely relative position on.
3. biology sensor, it comprises having and is branched off into a plurality of the 1st effect utmost points and is branched off into the 1st pair of a plurality of utmost points, each branch tablet is replaced the 1st insulativity substrate of arranging, have and be branched off into the 2nd a plurality of effect utmost points and be branched off into the 2nd pair of a plurality of utmost points, each branch tablet is replaced the 2nd insulativity substrate of arranging, contain the reagent system of oxidoreducing enzyme and electron transfer mediator and be formed on sample supply path between the 1st and the 2nd insulated substrate, the 1st effect utmost point of in the sample supply path, alternately arranging and the branch tablet of the 1st pair of utmost point, the 2nd effect utmost point of alternately arranging and the branch tablet of the 2nd pair of utmost point and reagent system expose.
4. biology sensor according to claim 3 is characterized in that, the 2nd pair of utmost point is configured on the position extremely relative with the 1st effect, and the 2nd effect utmost point be configured in the 1st pair of extremely relative position on.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001161244 | 2001-05-29 | ||
| JP161244/2001 | 2001-05-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1463361A CN1463361A (en) | 2003-12-24 |
| CN1205474C true CN1205474C (en) | 2005-06-08 |
Family
ID=19004550
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB028018796A Expired - Lifetime CN1205474C (en) | 2001-05-29 | 2002-05-27 | Biosensor |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7022218B2 (en) |
| EP (1) | EP1288654B1 (en) |
| JP (1) | JP3690683B2 (en) |
| CN (1) | CN1205474C (en) |
| DE (1) | DE60229476D1 (en) |
| ES (1) | ES2315407T3 (en) |
| WO (1) | WO2002097418A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101571535A (en) * | 2008-01-30 | 2009-11-04 | 韩国科学技术研究院 | Biosensor containing 3-dimensional metal nano-wire electrode which forms nano channel, manufacturing method and bio-disc system containing the biosensor |
Families Citing this family (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6036924A (en) | 1997-12-04 | 2000-03-14 | Hewlett-Packard Company | Cassette of lancet cartridges for sampling blood |
| US7407811B2 (en) * | 1997-12-22 | 2008-08-05 | Roche Diagnostics Operations, Inc. | System and method for analyte measurement using AC excitation |
| US7390667B2 (en) * | 1997-12-22 | 2008-06-24 | Roche Diagnostics Operations, Inc. | System and method for analyte measurement using AC phase angle measurements |
| US8071384B2 (en) | 1997-12-22 | 2011-12-06 | Roche Diagnostics Operations, Inc. | Control and calibration solutions and methods for their use |
| US6391005B1 (en) | 1998-03-30 | 2002-05-21 | Agilent Technologies, Inc. | Apparatus and method for penetration with shaft having a sensor for sensing penetration depth |
| US20050103624A1 (en) * | 1999-10-04 | 2005-05-19 | Bhullar Raghbir S. | Biosensor and method of making |
| US7073246B2 (en) | 1999-10-04 | 2006-07-11 | Roche Diagnostics Operations, Inc. | Method of making a biosensor |
| US6540890B1 (en) | 2000-11-01 | 2003-04-01 | Roche Diagnostics Corporation | Biosensor |
| US8641644B2 (en) | 2000-11-21 | 2014-02-04 | Sanofi-Aventis Deutschland Gmbh | Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means |
| DE10058397A1 (en) * | 2000-11-24 | 2002-06-06 | Siemens Ag | Arrangement for an electrochemical analysis method and its use |
| US7025774B2 (en) | 2001-06-12 | 2006-04-11 | Pelikan Technologies, Inc. | Tissue penetration device |
| US9795747B2 (en) | 2010-06-02 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Methods and apparatus for lancet actuation |
| US7981056B2 (en) | 2002-04-19 | 2011-07-19 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
| US9226699B2 (en) | 2002-04-19 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling module with a continuous compression tissue interface surface |
| US8337419B2 (en) | 2002-04-19 | 2012-12-25 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| US7682318B2 (en) | 2001-06-12 | 2010-03-23 | Pelikan Technologies, Inc. | Blood sampling apparatus and method |
| EP1404233B1 (en) | 2001-06-12 | 2009-12-02 | Pelikan Technologies Inc. | Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties |
| ATE497731T1 (en) | 2001-06-12 | 2011-02-15 | Pelikan Technologies Inc | DEVICE FOR INCREASING THE SUCCESS RATE OF BLOOD YIELD OBTAINED BY A FINGER PICK |
| EP1404235A4 (en) | 2001-06-12 | 2008-08-20 | Pelikan Technologies Inc | Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge |
| JP4149911B2 (en) | 2001-06-12 | 2008-09-17 | ペリカン テクノロジーズ インコーポレイテッド | Electric lancet actuator |
| US9427532B2 (en) | 2001-06-12 | 2016-08-30 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| US6814844B2 (en) * | 2001-08-29 | 2004-11-09 | Roche Diagnostics Corporation | Biosensor with code pattern |
| US20060006141A1 (en) * | 2001-11-16 | 2006-01-12 | Stefan Ufer | Biomedical electrochemical sensor array and method of fabrication |
| US7717863B2 (en) | 2002-04-19 | 2010-05-18 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US9248267B2 (en) | 2002-04-19 | 2016-02-02 | Sanofi-Aventis Deustchland Gmbh | Tissue penetration device |
| US7291117B2 (en) | 2002-04-19 | 2007-11-06 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US8784335B2 (en) | 2002-04-19 | 2014-07-22 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling device with a capacitive sensor |
| US7901362B2 (en) | 2002-04-19 | 2011-03-08 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7648468B2 (en) | 2002-04-19 | 2010-01-19 | Pelikon Technologies, Inc. | Method and apparatus for penetrating tissue |
| US9795334B2 (en) | 2002-04-19 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US7892183B2 (en) | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
| US8579831B2 (en) | 2002-04-19 | 2013-11-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US7547287B2 (en) | 2002-04-19 | 2009-06-16 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US8221334B2 (en) | 2002-04-19 | 2012-07-17 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
| US7175642B2 (en) | 2002-04-19 | 2007-02-13 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
| US8702624B2 (en) | 2006-09-29 | 2014-04-22 | Sanofi-Aventis Deutschland Gmbh | Analyte measurement device with a single shot actuator |
| US7229458B2 (en) | 2002-04-19 | 2007-06-12 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US9314194B2 (en) | 2002-04-19 | 2016-04-19 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| US7232451B2 (en) | 2002-04-19 | 2007-06-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7491178B2 (en) | 2002-04-19 | 2009-02-17 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US8267870B2 (en) | 2002-04-19 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for body fluid sampling with hybrid actuation |
| US7976476B2 (en) | 2002-04-19 | 2011-07-12 | Pelikan Technologies, Inc. | Device and method for variable speed lancet |
| US7331931B2 (en) | 2002-04-19 | 2008-02-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7297122B2 (en) | 2002-04-19 | 2007-11-20 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7674232B2 (en) | 2002-04-19 | 2010-03-09 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7371247B2 (en) | 2002-04-19 | 2008-05-13 | Pelikan Technologies, Inc | Method and apparatus for penetrating tissue |
| US7909778B2 (en) | 2002-04-19 | 2011-03-22 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
| US7226461B2 (en) | 2002-04-19 | 2007-06-05 | Pelikan Technologies, Inc. | Method and apparatus for a multi-use body fluid sampling device with sterility barrier release |
| AT411627B (en) * | 2002-08-23 | 2004-03-25 | Hoffmann La Roche | DEVICE FOR CHECKING THE POSITIONING AND BUBBLE CLEARANCE OF A MEDICAL MICRO SAMPLE IN A FLOW MEASURING CELL |
| EP1583950B1 (en) | 2002-12-26 | 2017-04-05 | Meso Scale Technologies, LLC. | Assay cartridges and methods of using the same |
| US8574895B2 (en) | 2002-12-30 | 2013-11-05 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus using optical techniques to measure analyte levels |
| CA2519267A1 (en) * | 2003-03-20 | 2004-09-30 | Asahi Kasei Life & Living Corporation | Oxygen indicator and package |
| US7850621B2 (en) | 2003-06-06 | 2010-12-14 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
| WO2006001797A1 (en) | 2004-06-14 | 2006-01-05 | Pelikan Technologies, Inc. | Low pain penetrating |
| US7597793B2 (en) * | 2003-06-20 | 2009-10-06 | Roche Operations Ltd. | System and method for analyte measurement employing maximum dosing time delay |
| US8206565B2 (en) | 2003-06-20 | 2012-06-26 | Roche Diagnostics Operation, Inc. | System and method for coding information on a biosensor test strip |
| US8071030B2 (en) | 2003-06-20 | 2011-12-06 | Roche Diagnostics Operations, Inc. | Test strip with flared sample receiving chamber |
| US8148164B2 (en) | 2003-06-20 | 2012-04-03 | Roche Diagnostics Operations, Inc. | System and method for determining the concentration of an analyte in a sample fluid |
| US7452457B2 (en) * | 2003-06-20 | 2008-11-18 | Roche Diagnostics Operations, Inc. | System and method for analyte measurement using dose sufficiency electrodes |
| US7645373B2 (en) * | 2003-06-20 | 2010-01-12 | Roche Diagnostic Operations, Inc. | System and method for coding information on a biosensor test strip |
| US7718439B2 (en) | 2003-06-20 | 2010-05-18 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
| ES2657627T3 (en) * | 2003-06-20 | 2018-03-06 | F. Hoffmann-La Roche Ag | Electrochemical biosensors |
| US8058077B2 (en) | 2003-06-20 | 2011-11-15 | Roche Diagnostics Operations, Inc. | Method for coding information on a biosensor test strip |
| CA2529378C (en) | 2003-06-20 | 2014-04-15 | F.Hoffmann-La Roche Ag | Method and reagent for producing narrow, homogenous reagent strips |
| US7645421B2 (en) * | 2003-06-20 | 2010-01-12 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
| US8679853B2 (en) * | 2003-06-20 | 2014-03-25 | Roche Diagnostics Operations, Inc. | Biosensor with laser-sealed capillary space and method of making |
| EP1671096A4 (en) | 2003-09-29 | 2009-09-16 | Pelikan Technologies Inc | Method and apparatus for an improved sample capture device |
| WO2005037095A1 (en) | 2003-10-14 | 2005-04-28 | Pelikan Technologies, Inc. | Method and apparatus for a variable user interface |
| EP3273232A2 (en) * | 2003-12-04 | 2018-01-24 | Panasonic Healthcare Holdings Co., Ltd. | Method of measuring blood component, sensor used in the method, and measuring device |
| KR101049330B1 (en) * | 2003-12-04 | 2011-07-13 | 파나소닉 주식회사 | Method for measuring hematocrit, sensor and measuring device used therein |
| US7822454B1 (en) | 2005-01-03 | 2010-10-26 | Pelikan Technologies, Inc. | Fluid sampling device with improved analyte detecting member configuration |
| US8668656B2 (en) | 2003-12-31 | 2014-03-11 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for improving fluidic flow and sample capture |
| EP3115777B1 (en) * | 2004-04-19 | 2020-01-08 | PHC Holdings Corporation | Method for measuring blood components |
| EP1751546A2 (en) | 2004-05-20 | 2007-02-14 | Albatros Technologies GmbH & Co. KG | Printable hydrogel for biosensors |
| WO2005120365A1 (en) | 2004-06-03 | 2005-12-22 | Pelikan Technologies, Inc. | Method and apparatus for a fluid sampling device |
| US7556723B2 (en) * | 2004-06-18 | 2009-07-07 | Roche Diagnostics Operations, Inc. | Electrode design for biosensor |
| US7569126B2 (en) | 2004-06-18 | 2009-08-04 | Roche Diagnostics Operations, Inc. | System and method for quality assurance of a biosensor test strip |
| GB0428130D0 (en) * | 2004-12-22 | 2005-01-26 | Oxford Biosensors Ltd | Selective HDL cholesterol assay |
| US8652831B2 (en) | 2004-12-30 | 2014-02-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for analyte measurement test time |
| US8057404B2 (en) * | 2005-10-12 | 2011-11-15 | Panasonic Corporation | Blood sensor, blood testing apparatus, and method for controlling blood testing apparatus |
| JP2008096235A (en) * | 2006-10-11 | 2008-04-24 | Sharp Corp | Electrochemical measuring microchip |
| KR100812691B1 (en) * | 2007-03-19 | 2008-03-13 | 영동제약 주식회사 | Biosensor using electro luminescence |
| CN101303347B (en) * | 2007-04-20 | 2013-07-31 | 天津亿朋医疗器械有限公司 | Biological sensor |
| WO2009015077A1 (en) * | 2007-07-23 | 2009-01-29 | Agamatrix, Inc. | Electrochemical test strip |
| AU2016200514B2 (en) * | 2007-07-23 | 2017-03-30 | Agamatrix, Inc. | Electrochemical test strip |
| AU2013204842B2 (en) * | 2007-07-23 | 2016-01-28 | Agamatrix, Inc. | Electrochemical test strip |
| CN101842698B (en) * | 2007-10-31 | 2016-06-15 | 爱科来株式会社 | Analytical tool |
| WO2009126900A1 (en) | 2008-04-11 | 2009-10-15 | Pelikan Technologies, Inc. | Method and apparatus for analyte detecting device |
| KR101003077B1 (en) | 2008-10-16 | 2010-12-21 | 세종공업 주식회사 | Electrochemical biosensor structure and measuring method using the same |
| JP5172606B2 (en) * | 2008-10-30 | 2013-03-27 | シスメックス株式会社 | Method and apparatus for specific detection of test substance, and test chip |
| US9375169B2 (en) | 2009-01-30 | 2016-06-28 | Sanofi-Aventis Deutschland Gmbh | Cam drive for managing disposable penetrating member actions with a single motor and motor and control system |
| US20110079522A1 (en) * | 2009-10-02 | 2011-04-07 | Lifescan Scotland Limited | Multi-analyte test strip with inline working electrodes and shared opposing counter/reference electrode |
| US8965476B2 (en) | 2010-04-16 | 2015-02-24 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
| US20120048746A1 (en) * | 2010-08-30 | 2012-03-01 | Cilag Gmbh International | Analyte test strip with electrically distinguishable divided electrode |
| CN103649742B (en) * | 2012-05-17 | 2015-11-25 | 松下知识产权经营株式会社 | Electrochemical detector and manufacture method thereof |
| MX2014015162A (en) * | 2012-06-28 | 2015-03-05 | Siemens Healthcare Diagnostics | Reader device and method of signal amplification. |
| JP6219315B2 (en) * | 2013-01-17 | 2017-10-25 | 田中貴金属工業株式会社 | Biosensor and manufacturing method thereof |
| US9945804B2 (en) * | 2014-07-17 | 2018-04-17 | Siemens Healthcare Diagnostics Inc. | Sensor array |
| WO2017120464A1 (en) * | 2016-01-08 | 2017-07-13 | Siemens Healthcare Diagnostics Inc. | Heating element for sensor array |
| JP2017138164A (en) * | 2016-02-02 | 2017-08-10 | 大日本印刷株式会社 | Electrode structure manufacturing method, sensor electrode manufacturing method, electrode structure, and sensor electrode |
| US20210255142A1 (en) * | 2018-07-09 | 2021-08-19 | National Institute For Materials Science | Diagnosing apparatus, analysis method, and program |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5001048A (en) * | 1987-06-05 | 1991-03-19 | Aurthur D. Little, Inc. | Electrical biosensor containing a biological receptor immobilized and stabilized in a protein film |
| JP2590002B2 (en) * | 1988-04-25 | 1997-03-12 | 日本電信電話株式会社 | Microelectrode cell for electrochemical measurement and method for producing the same |
| JP2517153B2 (en) | 1989-09-21 | 1996-07-24 | 松下電器産業株式会社 | Biosensor and manufacturing method thereof |
| GB9218376D0 (en) * | 1992-08-28 | 1992-10-14 | Cranfield Inst Of Tech | Media for biocatalytic electrochemical reactions in the gaseous phase |
| DE4318519C2 (en) * | 1993-06-03 | 1996-11-28 | Fraunhofer Ges Forschung | Electrochemical sensor |
| JPH09159644A (en) * | 1995-12-11 | 1997-06-20 | Dainippon Printing Co Ltd | Biosensor and manufacture thereof |
| JPH09243590A (en) * | 1996-03-08 | 1997-09-19 | Tdk Corp | Micro comb-shaped electrode and its manufacture and electrode unit for electrochemical measurement of solution system |
| JPH1164271A (en) | 1997-08-18 | 1999-03-05 | Nagoyashi | Current amplification type oxyzen sensor |
| JP2000065777A (en) * | 1998-08-21 | 2000-03-03 | Nok Corp | Biosensor |
| JP3267936B2 (en) * | 1998-08-26 | 2002-03-25 | 松下電器産業株式会社 | Biosensor |
| US6338790B1 (en) * | 1998-10-08 | 2002-01-15 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
| JP2000121593A (en) * | 1998-10-13 | 2000-04-28 | Omron Corp | Enzyme electrode |
| DE19916921A1 (en) | 1999-04-14 | 2000-10-19 | Fraunhofer Ges Forschung | Electrical sensor array |
-
2002
- 2002-05-27 US US10/333,232 patent/US7022218B2/en not_active Expired - Lifetime
- 2002-05-27 JP JP2003500548A patent/JP3690683B2/en not_active Expired - Lifetime
- 2002-05-27 EP EP02774074A patent/EP1288654B1/en not_active Expired - Lifetime
- 2002-05-27 DE DE60229476T patent/DE60229476D1/en not_active Expired - Lifetime
- 2002-05-27 ES ES02774074T patent/ES2315407T3/en not_active Expired - Lifetime
- 2002-05-27 WO PCT/JP2002/005129 patent/WO2002097418A1/en active Application Filing
- 2002-05-27 CN CNB028018796A patent/CN1205474C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101571535A (en) * | 2008-01-30 | 2009-11-04 | 韩国科学技术研究院 | Biosensor containing 3-dimensional metal nano-wire electrode which forms nano channel, manufacturing method and bio-disc system containing the biosensor |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1288654A1 (en) | 2003-03-05 |
| US20040005721A1 (en) | 2004-01-08 |
| WO2002097418A1 (en) | 2002-12-05 |
| CN1463361A (en) | 2003-12-24 |
| EP1288654B1 (en) | 2008-10-22 |
| EP1288654A4 (en) | 2003-07-02 |
| US7022218B2 (en) | 2006-04-04 |
| ES2315407T3 (en) | 2009-04-01 |
| JP3690683B2 (en) | 2005-08-31 |
| DE60229476D1 (en) | 2008-12-04 |
| JPWO2002097418A1 (en) | 2004-09-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1205474C (en) | Biosensor | |
| CN100339701C (en) | Biosensor | |
| CN1134659C (en) | Biosensor | |
| CN1122178C (en) | Substrate determining method | |
| CN1142427C (en) | Biological sensor | |
| CN1227525C (en) | Biosensor | |
| Slaughter et al. | Highly selective and sensitive self-powered glucose sensor based on capacitor circuit | |
| CN1162699C (en) | Biosensor | |
| CN1239901C (en) | Biological sensor | |
| CN1172181C (en) | Biological sensor | |
| JP3947356B2 (en) | Microsphere-containing sensor | |
| JP4814953B2 (en) | Method for measuring hematocrit value of blood sample, method for measuring concentration of analyte in blood sample, sensor chip and sensor unit | |
| JPH01291153A (en) | Biosensor | |
| JP2005003679A (en) | Electrochemical biosensor | |
| JPWO2008047842A1 (en) | Method for measuring hematocrit value of blood sample, method for measuring concentration of analyte in blood sample, sensor chip and sensor unit | |
| JP2009250806A (en) | Biosensor system, sensor chip and measuring method of concentration of analyte in blood sample | |
| Bilitewski et al. | Glucose biosensors based on thick film technology | |
| CN1289905C (en) | Biological sensor, and adaptor and measuring equipment used for the same | |
| JP3528529B2 (en) | Biosensor | |
| JP2007298325A (en) | Electrode chip and manufacturing method therefor | |
| JP2006275818A (en) | Biosensor | |
| KR100739865B1 (en) | Bio-sensor | |
| JP2004226358A (en) | Biosensor | |
| CN215218661U (en) | Electrochemical sensor array capable of simultaneously detecting creatinine, glucose and uric acid | |
| CN1296180A (en) | Biochemical sensor with multifunction sampling mode |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: PANASONIC HEALTHCARE + MEDICAL EQUIPMENT CO., LTD. Free format text: FORMER OWNER: MATSUSHITA ELECTRIC INDUSTRIAL CO, LTD. Effective date: 20140521 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20140521 Address after: Ehime Prefecture, Japan Patentee after: Panasonic Healthcare Co., Ltd Address before: Japan Osaka kamato City Patentee before: Matsushita Electric Industrial Co., Ltd. |
|
| ASS | Succession or assignment of patent right |
Owner name: PANASONIC HEALTHCARE HOLDINGS CO., LTD. Free format text: FORMER OWNER: PANASONIC HEALTHCARE + MEDICAL EQUIPMENT CO., LTD. Effective date: 20150401 |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150401 Address after: Tokyo, Japan Patentee after: Panasonic's health medical treatment is controlled interest Co., Ltd. Address before: Ehime Prefecture, Japan Patentee before: Panasonic Healthcare Co., Ltd |
|
| CP01 | Change in the name or title of a patent holder |
Address after: Tokyo, Japan Patentee after: Pu Hei holding company Address before: Tokyo, Japan Patentee before: Panasonic's health medical treatment is controlled interest Co., Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CX01 | Expiry of patent term |
Granted publication date: 20050608 |
|
| CX01 | Expiry of patent term |